Effects of Closed-loop Automatic Control of FiO2 in Extremely Preterm Infants

Condition(s) studied

Investigational drug(s) / intervention(s)

closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C): Application of FiO2-C (provided by standard infant ventilators) in addition to manual adjustments of the inspired oxygen fraction (FiO2) during mechanical ventilation and continuous positive airway pressure (CPAP) in ELGANs at least up to 32weeks PMA according to a standardized protocol

Study summary

Extremely low gestational age neonates (ELGANs), i.e. those born at \<28 weeks, frequently experience intermittent hypoxemic/hyperoxemic episodes. Observational data indicate that severe and prolonged hypoxemic episodes are associated with retinopathy of prematurity (ROP), impaired long-term development and death. Closed-loop automated control of the inspiratory fraction of oxygen (FiO2-C) reduces time outside the oxygen target range, decreases number and duration of hypo- and hyperoxemic episodes, and reduces caregivers' workload. The proposed observer-blinded randomized controlled trial was designed and will be powered to compare the effect of FiO2-C in addition to manual adjustments, in comparison with manual adjustments of FiO2 only, on death and severe complications of prematurity thought to be related to hypoxia/hyperoxia and neurodevelopmental impairment in ELGANs. The results of this trial may help to improve the quality of life of ELGANs and reduce the burden of significant morbidity as well as costs for health care and society

Eligibility

Primary outcome measure(s)

• Primary outcome I: composite outcome of death, severe retinopathy of prematurity (ROP), chronic lung disease of prematurity (BPD), necrotizing enterocolitis (NEC) — until/at post-menstrual age (PMA) 36 weeks (death, BPD and NEC) and at latest at PMA 44 weeks for severity of ROP
  The primary outcome I is a composite of any of the following: * Death * Severe retinopathy of prematurity (severe ROP, as defined in 7.3.1) * Chronic lung disease of prematurity (BPD, according to the physiological definition, which is described in detail in the study protocol) * Necrotizing enterocolitis (NEC, as defined in the study protocol) until discharge from hospital The primary endpoint I will be analysed between the two intervention groups using a stratified chi2-test and Cochrane Mantel-Haenszel statistics will be presented (risk ratios and 95%-confidence intervals). The factors considered for randomization (center, sex and gestational age at birth (\<26 weeks and ≥26 weeks) will also be used for analysis.
• Primary outcome II: composite of death or neurodevelopmental impairment (NDI) — at 24 months of age corrected for prematurity
  The primary outcome II is a composite of any of the following: • death or neurodevelopmental impairment (defined as at least one of the following components: motor disability (GMFCS 2-5), language or cognitive delay (language composite score \< 85 or cognitive composite score \< 85 on Bayley Scales of Infant Development, 3rd edition) or severe visual or hearing impairment (need for a hearing aid or cochlear implant)). In case of missing Bayley III test results, Bayley II results, other developmental test results or PARCA-R parent questionnaire results may substitute for the Bayley III test results in a hierarchical manner described in the study protocol. The primary outcome II will be analysed between the two intervention groups using chi2-test and Cochrane Mantel-Haenszel statistics will be presented (risk ratios and 95%-confidence intervals). The factors considered for randomization (center, sex and gestational age at birth (\<26 weeks and ≥26 weeks) will also be used for analysis.

Trial sites (32)